Epigenetic age is associated with baseline and 3-year change in frailty in the Canadian Longitudinal Study on Aging
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Background: The trajectory of frailty in older adults is important to public health; therefore, markers that may help predict this and other important outcomes could be beneficial. Epigenetic clocks have been developed and are associated with various health-related outcomes and sociodemographic factors, but associations with frailty are poorly described. Further, it is uncertain whether newer generations of epigenetic clocks, trained on variables other than chronological age, would be more strongly associated with frailty than earlier developed clocks. Using data from the Canadian Longitudinal Study on Aging (CLSA), we tested the hypothesis that clocks trained on phenotypic markers of health or mortality (i.e., Dunedin PoAm, GrimAge, PhenoAge and Zhang in Nat Commun 8:14617, 2017) would best predict changes in a 76-item frailty index (FI) over a 3-year interval, as compared to clocks trained on chronological age (i.e., Hannum in Mol Cell 49:359–367, 2013, Horvath in Genome Biol 14:R115, 2013, Lin in Aging 8:394–401, 2016, and Yang Genome Biol 17:205, 2016). Results: We show that in 1446 participants, phenotype/mortality-trained clocks outperformed age-trained clocks with regard to the association with baseline frailty (mean = 0.141, SD = 0.075), the greatest of which is GrimAge, where a 1-SD increase in ΔGrimAge (i.e., the difference from chronological age) was associated with a 0.020 increase in frailty (95% CI 0.016, 0.024), or ~ 27% relative to the SD in frailty. Only GrimAge and Hannum (Mol Cell 49:359–367, 2013) were significantly associated with change in frailty over time, where a 1-SD increase in ΔGrimAge and ΔHannum 2013 was associated with a 0.0030 (95% CI 0.0007, 0.0050) and 0.0028 (95% CI 0.0007, 0.0050) increase over 3 years, respectively, or ~ 7% relative to the SD in frailty change. Conclusion: Both prevalence and change in frailty are associated with increased epigenetic age. However, not all clocks are equally sensitive to these outcomes and depend on their underlying relationship with chronological age, healthspan and lifespan. Certain clocks were significantly associated with relatively short-term changes in frailty, thereby supporting their utility in initiatives and interventions to promote healthy aging.
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The DNAm GrimAge clock shows consistently stronger associations with various measures of age-related dysfunction, including heart disease, frailty, and cognitive and physical decline, compared to other clocks.
“The DNAm GrimAge clock shows consistently stronger associations with various measures of age-related dysfunction, including heart disease, frailty, and cognitive and physical decline, compared to other clocks47,48,50,64–72.”
From Measuring biological age using omics data (2022) · cites this paper as [64]
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Measuring biological age using omics data
Rutledge, J., Oh, H., & Wyss-Coray, T. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00511-7 · Cited by 570 · see citing works
- Authors
- Verschoor, C. P., Lin, D. T. S., Kobor, M. S., Mian, O., Ma, J., Pare, G., & Ybazeta, G.
- Affiliations
- Health Sciences North (CA)
- University of British Columbia (CA)
- McMaster University (CA)
- Corresponding author
- Verschoor, Chris P.
- Venue
- Clinical Epigenetics
- Published
- 2021-08-23
- Volume
- 13
- Issue
- 1
- Pages
- 163-163
- ISSN
- 1868-7075 (ISSN-L)
- 1868-7083
- PMC
- PMC8381580
- OpenAlex
- W3193863613
- Cited by
- 58
- References
- 67
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 6 · 2023: 16 · 2022: 12
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical Epigenetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- cIRcle (University of British Columbia) (submittedVersion, cc-by)
- Funders
- Institute of Aging (ACD-170293)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- epigenetic clocks, biological age, frailty, frailty index, GrimAge, Hannum clock, Horvath clock, PhenoAge, chronological age, older adults, Canadian Longitudinal Study on Aging
- MeSH terms
- Frailty, Sociodemographic Factors, Age Factors, Aged, Aged, 80 and over, Aging, Canada, Cause of Death, Female, Humans, Longitudinal Studies, Male, Middle Aged, Time Factors, Genetic Variation, DNA Methylation, Epigenesis, Genetic
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